This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Our research at NECAT aims to decipher the gating mechanisms and pharmacological properties of various eukaryotic K+ ion channels. The first channel is the voltage-dependent K+ channel, which opens in response to changes in membrane voltage and is responsible for producing electrical signals in brain cells. We are aiming to determine structures of intermediate gating states to understand how membrane voltage drives the channel between closed and opened conformations. The second channel is the eukaryotic inward rectifier K+ channel, which controls the resting membrane potential in many neurons. The third channel is the G-protein-gated channel, which opens in response to the stimulation of G-proteins signaling pathways. This channel type regulates heart rate, among other processes, and is an important potential target for the treatment of atrial fibrillation. The fourth channel is the high-condcutance Ca2+and voltage-dependent K+ channel. This channel functions in various cell types, including vascular and airway smooth muscle. It is a potential target for the treatment of hypertension and asthma.